**8.1 Gestational Diabetes Mellitus (GDM)**

Normal pregnancy is characterized by approximately 50% decrease in insulinmediated glucose disposal in humans and a 200–250% increase in insulin secretion to maintain euglycaemia in the mother [81]. Women with adequate insulin secreting capacity overcome this insulin resistance of pregnancy by secreting more endogenous insulin to maintain normal blood glucose. In a study involving

#### *Oral Glucose Tolerance Test (OGTT): Undeniably the First Choice Investigation… DOI: http://dx.doi.org/10.5772/intechopen.96549*

non-GDM pregnancies, plasma glucose levels during late pregnancy (mean 1 SD) were noted to be fasting 3.9 0.4 mmol/L, 1 hour postprandial 6.1 0.7 mmol/L, and 2 hours postprandial 5.5 0.6 mmol/L with a mean glucose of 4.9 0.6 mmol/ L [82]**.** The HAPO study reported a mean fasting glucose of 4.5 0.4 mmol/L, derived from 23316 pregnant women [38]. But women with diabetes or those who have tendency to develop GDM, endogenous insulin secretion is inadequate to compensate for the insulin resistance (IR), hence their hyperglycaemia worsen or they development hyperglycaemia.

Numerous factors such as placental hormones, obesity, inactivity, an unhealthy diet, genetic and epigenetic contributions influence IR in pregnancy, but the causal mechanisms are complex and still not completely elucidated [83]. Placental derived hormones are believed to be a major factor in reprogramming maternal physiology to achieve an I-R state. Human placental lactogen (hPL) and human placental growth hormone (hPGH) are the major player in pregnancy induced IR [84]. Prolactin, progesterone, estradiol and cortisol are increased during pregnancy and may contribute to the development of IR in pregnancy [85]**.** Recently, studies have implicated adiponectin from adipocytes and secreted factors, such as TNF-α, leptin, IL-6, resistin in mediating IR of pregnancy [86]. Most women who develop GDM have increased IR caused by alteration in insulin signaling pathway, abnormal subcellular localization of GLUT4 transporters, increased expression of the membrane glycoprotein PC-1 or reduced insulin-mediated glucose transport. GDM is usually diagnosed after 20 weeks' gestation when placental hormones are increase substantially as the placental size increases.

In 2014, the WHO has defined hyperglycaemia in pregnancy (HIP) as diabetes first detected at any time during pregnancy, along with pre-existing diabetes and is further sub-classified as diabetes in pregnancy (DIP) and gestational diabetes mellitus (GDM**)** [87]**.** Nowadays type 2 diabetes is frequently found in young women due to ongoing epidemics of obesity therefore the number of undiagnosed (before pregnancy) is increasing. Screening for GDM earlier than 24-28 weeks in identifying these young women and address perinatal risks that may be particular to their greater degree of hyperglycaemia is becoming more important because of the following [87]:


How then do we identify these women? Early glucose testing is important. Usually in early part of pregnancy (e.g. first trimester and first half of second trimester) fasting and postprandial glucose concentrations are normally lower than in normal due to less effect of placental hormone and decreased appetite, compared to non–diabetes women. Elevated fasting or postprandial plasma glucose levels at this time in pregnancy may reflect diabetes antedating pregnancy. In this regards there was a uniform agreement during IADPSG Pasadena meeting that this assessment should be made during the initial visit for prenatal care. However, there is variability in time of enrollment for prenatal care beyond the control of health care providers. Accordingly, no limit can be place on the timing of initial assessment for

**7.4 Testing of children for type 2 diabetes mellitus**

*Type 2 Diabetes - From Pathophysiology to Cyber Systems*

in children at risk of glucose intolerance is necessary.

percentile, or weight >120% of ideal for height)

1.Plus any two of the following risk factors

2.Family history of Type 2 DM, 1o or 2o

3.Native American, black, Asian, Latino

c. Age of initiation: 10 years or onset of puberty

b. Signs of insulin resistance (acanthosis nigricans, hypertension,

family about the procedure and answer any questions they may ask.

*7.4.1 Criteria/indications*

dyslipidaemia)

e. Test: FPG preferred

**dysglycaemia of GDM**

**130**

**8.1 Gestational Diabetes Mellitus (GDM)**

d. Frequency: every two years

Until recently, type 1 diabetes was the most frequent form of diabetes among young people [80]. Recently however, there are increasing reports of T2DM, previously a disorder of middle-aged or elderly persons among children and adolescents. In the 1990s, various reports indicated that the incidence of childhood type 2 diabetes was increasing and this trend continues at present. The ADA and the American Academic of Paediatrics approved screening for T2DM in children because T2DM can be asymptomatic at diagnosis and requires tight glycaemic control to delay the onset of chronic vascular complications. Several studies have shown an increased risk of microvascular complications among young adolescents with T2DM compared to those with T1DM. Therefore, screening for IGT and T2DM

a. Overweight (BMI ≥ 85th percentile for age and sex, weight for height ≥ 85th

The dose of glucose is weight dependent-1.75 g/kg body weight. The maximum load is 75 g. Lucozade may be given instead which is more palatable. Formulation 73 kcal carbohydrate/100 ml, gives 75 g glucose in 419 ml Maximum dose is 75 g. Apply ametop gel 45 minutes prior to cannulations to ensure the area is numbed. Utilize a member of the play team to prepare the child for the procedure and provide distractive techniques throughout. Give full explanations to the child and

**8. OGTT in gestation diabetes mellitus, an undeniably the only test for**

Normal pregnancy is characterized by approximately 50% decrease in insulinmediated glucose disposal in humans and a 200–250% increase in insulin secretion to maintain euglycaemia in the mother [81]. Women with adequate insulin secreting capacity overcome this insulin resistance of pregnancy by secreting more endogenous insulin to maintain normal blood glucose. In a study involving

detection of overt diabetes in pregnancy. It was advised that selective, stepwise screening particularly in the low- and mid-income countries is more cost effective. This entail: (a) Categorizing all women at first antenatal visit into low, moderate and high risk of GDM; (b) Those in moderate to high risk groups should have glucose challenge test with 50 g anhydrous glucose diluted in 150 ml of water to drink and venous sample is taken at 1-hr. If result is 7.8 (7.2) mmol/L, at first visit, proceed to diagnostic OGTT. If result is negative repeat glucose challenge test at 24–28 weeks of gestation; (c) Those in low risk group should be screening only at 24–28 weeks of gestation. However, if enrollment is at 24 weeks gestation or later and overt diabetes is not found, the initial test should be either 50 g glucose challenge first or the 75-g OGTT. Although IAFPSG Consensus Panel members favored use of A1c at first visit, this is not feasible in most low- and mid-income countries. It was also recommended that an FPG value in early pregnancy ≥5.1 mmol/L (92 mg/dl) also be classified as GDM.

and child. The goal of screening therefore is to reduce maternal and fetal complications such as preeclampsia, caesarean delivery, congenital malformations, macrosomia, shoulder dystocia, nerve palsy, bone fracture, hyperbilirubinaemia and infant death, or later childhood/adolescent overweight as demonstrated in some studies. The Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) [94], showed a 4% reduction in the composite outcome of severe perinatal complications (death, shoulder dystocia, bone fracture, nerve palsy) among women randomized to routine care compared with 1% among the intervention group, while in the National Institute of Child Health and Human Development (NICHD) study, though there was no reduction in the composite primary

*Oral Glucose Tolerance Test (OGTT): Undeniably the First Choice Investigation…*

*DOI: http://dx.doi.org/10.5772/intechopen.96549*

outcome (perinatal mortality, birth trauma and neonatal hypoglycaemia, hyperbilirubinaemia, or hyperinsulinaemia), there was reductions in fetal overgrowth, shoulder dystocia, caesarean section delivery and pre-eclampsia. During pregnancy, gestational diabetes requires treatment to normalize maternal blood glucose levels to avoid complications in both the infant and the mother. Untreated hyperglycaemia in pregnancy may result into either or all of the following com-

euglycaemia in labour reduces the risk of hypoglycaemia, hypocalcaemia, hyperbilirubinaemia and polycythemia in the baby. In addition, the maternal metabolic milieu was identified as a key determinant for the susceptibility to obesity, metabolic syndrome and T2DM in the offspring, a phenomenon often described as 'fetal programming'. A study showed that infant of GDM were followed biennially from the age of 5 years using 75 g 2-hr OGTT among the Pima Indians in Arizona, USA, and Diabetes developed in the next generation in 6.9% and 30.1% of breast-fed offspring of non-diabetic and diabetic women, respectively and in 11.9% and 43.6% of bottle-fed offspring, respectively. Shoulder dystocia (SD) occurs in 1–2% of pregnancies, with majority of cases occurring in non-macrosomic fetuses, however, it increased for all birth weights, with a threefold increase when birth weight is >4000 g. Brachial plexus injury (BPI) occurs in 0.06%–0.26% of normal deliveries but occurs in 16–23% of births complicated by shoulder dystocia. GDM is an independent risk factor for BPI with a relative risk of 1.9–3.19 but in only 6–10%% of BPI is maternal GDM documented. It can be inferred therefore that the incidence of adverse perinatal outcomes increases

as glucose intolerance increases, that identification of women with

hyperglycaemia in pregnancy has clinical significance. As hyperglycaemia in pregnancy is an asymptomatic condition, diagnosis is dependent on some form of

> a. Respiratory distress in the baby, and associated feeding problems b. Pregnancy induced hypertension, Pre-eclampsia and eclampsia c. The risk of developing diabetes later in life or in a future pregnancy is

d. Haemorrhage and preterm delivery e. Sevenfold higher risk of the mother developing T2DM after pregnancy f. Increase chances of death in both mother and the baby

increased

About 10–25% of infants born of GDM pregnancies are macrosomic; maternal

plications in **Table 7**.

screening.

**Table 7.**

**133**

a. Placenta abruption b. Premature delivery

ethnicity)

c. Shoulder dystocia and Brachial plexus injury d. Macrosomic baby (weight ≥ 4 kg) or weight of >90th centile for gestational(according to

e. Baby is prone to hypoglycaemia f. Hyperbilirubinaemia

g. Increase tendency of assisted delivery, Caesarean section, or induction of labour

*Complications of GDM if it is not diagnosed or properly managed [95].*

Determining prevalence of GDM is difficult due to inconsistencies in screening methods. Because the IADPSG's is stricter when applied by IDF about 14% of 18 million live births were affected by gestational diabetes mellitus, where South-East Asia had the highest prevalence of GDM at 24.2% and the lowest was in Africa at 10.5% [88]. Almost 90% of cases of hyperglycaemia in pregnancy occurred in lowand middle-income countries, where access to maternal healthcare is limited. In Nigeria, the prevalence of HIP is projected to be 13.9%, and age-adjusted prevalence of 37.5% (crude 41.0%) in the United Arab Emirates is note [89]. The incidence of GDM has increased over the past decades in parallel with the increase in rates of obesity and type 2 diabetes mellitus, and this trend is expected to continue. GDM affects 7% of all pregnancies worldwide, 1.1% to 14.3% in USA, 3.8% to 6.5% in Canada, 6–9% in India. It is diagnosed at 16.3% in ≤16 weeks of gestation, 22.4% between 17 and 23 weeks and 61.3% after 23 weeks of gestation [90]**.** It occurs more frequently among African Americans, Hispanic/Latino Americans, and American Indians. It is also more common among obese women and women with a family history of diabetes. After delivery, GDM will follow 1 of 3 clinical courses [91, 92]:


GDM has about 20–50% chance of developing type 2 diabetes in about 5– 10 years even when there is lack of signs and symptoms of diabetes. The enormity defers among different ethnic groups, ranging from 9% in Caucasians, 11.9% in Latinos, and 25% in women of Mediterranean or east-Asian descent [93]. When GDM women were followed for a longer period, higher incidence of type 2 diabetes after index pregnancies was noted in 40% while there are evidence rates as high as 70% in Canadian Aboriginal women [93].

#### **8.2 Should we then screen for GDM**

Screening and diagnosis of GDM and treating it effectively not only prevent adverse maternal and perinatal outcome but also future diabetes in both mother *Oral Glucose Tolerance Test (OGTT): Undeniably the First Choice Investigation… DOI: http://dx.doi.org/10.5772/intechopen.96549*

and child. The goal of screening therefore is to reduce maternal and fetal complications such as preeclampsia, caesarean delivery, congenital malformations, macrosomia, shoulder dystocia, nerve palsy, bone fracture, hyperbilirubinaemia and infant death, or later childhood/adolescent overweight as demonstrated in some studies. The Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) [94], showed a 4% reduction in the composite outcome of severe perinatal complications (death, shoulder dystocia, bone fracture, nerve palsy) among women randomized to routine care compared with 1% among the intervention group, while in the National Institute of Child Health and Human Development (NICHD) study, though there was no reduction in the composite primary outcome (perinatal mortality, birth trauma and neonatal hypoglycaemia, hyperbilirubinaemia, or hyperinsulinaemia), there was reductions in fetal overgrowth, shoulder dystocia, caesarean section delivery and pre-eclampsia. During pregnancy, gestational diabetes requires treatment to normalize maternal blood glucose levels to avoid complications in both the infant and the mother. Untreated hyperglycaemia in pregnancy may result into either or all of the following complications in **Table 7**.

About 10–25% of infants born of GDM pregnancies are macrosomic; maternal euglycaemia in labour reduces the risk of hypoglycaemia, hypocalcaemia, hyperbilirubinaemia and polycythemia in the baby. In addition, the maternal metabolic milieu was identified as a key determinant for the susceptibility to obesity, metabolic syndrome and T2DM in the offspring, a phenomenon often described as 'fetal programming'. A study showed that infant of GDM were followed biennially from the age of 5 years using 75 g 2-hr OGTT among the Pima Indians in Arizona, USA, and Diabetes developed in the next generation in 6.9% and 30.1% of breast-fed offspring of non-diabetic and diabetic women, respectively and in 11.9% and 43.6% of bottle-fed offspring, respectively. Shoulder dystocia (SD) occurs in 1–2% of pregnancies, with majority of cases occurring in non-macrosomic fetuses, however, it increased for all birth weights, with a threefold increase when birth weight is >4000 g. Brachial plexus injury (BPI) occurs in 0.06%–0.26% of normal deliveries but occurs in 16–23% of births complicated by shoulder dystocia. GDM is an independent risk factor for BPI with a relative risk of 1.9–3.19 but in only 6–10%% of BPI is maternal GDM documented. It can be inferred therefore that the incidence of adverse perinatal outcomes increases as glucose intolerance increases, that identification of women with hyperglycaemia in pregnancy has clinical significance. As hyperglycaemia in pregnancy is an asymptomatic condition, diagnosis is dependent on some form of screening.


*Complications of GDM if it is not diagnosed or properly managed [95].*

detection of overt diabetes in pregnancy. It was advised that selective, stepwise screening particularly in the low- and mid-income countries is more cost effective. This entail: (a) Categorizing all women at first antenatal visit into low, moderate and high risk of GDM; (b) Those in moderate to high risk groups should have glucose challenge test with 50 g anhydrous glucose diluted in 150 ml of water to drink and venous sample is taken at 1-hr. If result is 7.8 (7.2) mmol/L, at first visit, proceed to diagnostic OGTT. If result is negative repeat glucose challenge test at 24–28 weeks of gestation; (c) Those in low risk group should be screening only at 24–28 weeks of gestation. However, if enrollment is at 24 weeks gestation or later and overt diabetes is not found, the initial test should be either 50 g glucose challenge first or the 75-g OGTT. Although IAFPSG Consensus Panel members favored use of A1c at first visit, this is not feasible in most low- and mid-income countries. It was also recommended that an FPG value in early pregnancy

Determining prevalence of GDM is difficult due to inconsistencies in screening methods. Because the IADPSG's is stricter when applied by IDF about 14% of 18 million live births were affected by gestational diabetes mellitus, where South-East Asia had the highest prevalence of GDM at 24.2% and the lowest was in Africa at 10.5% [88]. Almost 90% of cases of hyperglycaemia in pregnancy occurred in lowand middle-income countries, where access to maternal healthcare is limited. In Nigeria, the prevalence of HIP is projected to be 13.9%, and age-adjusted prevalence of 37.5% (crude 41.0%) in the United Arab Emirates is note [89]. The incidence of GDM has increased over the past decades in parallel with the increase in rates of obesity and type 2 diabetes mellitus, and this trend is expected to continue. GDM affects 7% of all pregnancies worldwide, 1.1% to 14.3% in USA, 3.8% to 6.5% in Canada, 6–9% in India. It is diagnosed at 16.3% in ≤16 weeks of gestation, 22.4% between 17 and 23 weeks and 61.3% after 23 weeks of gestation [90]**.** It occurs more frequently among African Americans, Hispanic/Latino Americans, and American Indians. It is also more common among obese women and women with a family history of diabetes. After delivery, GDM will follow 1 of 3 clinical courses [91, 92]:

a. Approximately 10% continue to have markedly abnormal glucose metabolism and fulfill criteria for diabetes in the nonpregnant adult these patients are

reclassified as having diabetes (Hyperglycaemia in pregnancy).

b. Approximately 5–10% of patients continue to exhibit abnormal glucose metabolism that is below diabetic levels. These patients are reclassified as

GDM has about 20–50% chance of developing type 2 diabetes in about 5– 10 years even when there is lack of signs and symptoms of diabetes. The enormity defers among different ethnic groups, ranging from 9% in Caucasians, 11.9% in Latinos, and 25% in women of Mediterranean or east-Asian descent [93]. When GDM women were followed for a longer period, higher incidence of type 2 diabetes after index pregnancies was noted in 40% while there are evidence rates as high as

Screening and diagnosis of GDM and treating it effectively not only prevent adverse maternal and perinatal outcome but also future diabetes in both mother

≥5.1 mmol/L (92 mg/dl) also be classified as GDM.

*Type 2 Diabetes - From Pathophysiology to Cyber Systems*

having IFG or IGT, as appropriate.

70% in Canadian Aboriginal women [93].

**8.2 Should we then screen for GDM**

**132**

c. The remainder exhibit normal glucose metabolism.
